The purpose of this project is the investigation of basic mechanisms associated with naturally occurring or artifically neurotoxin-induced neurological diseases through the use of animal models and in vitro experiments. Interactions of various neuroactive drugs and neurotoxins with neurotransmitters in the central nervous system have provided the focus for combined behavioral and neurochemicalk studies emphasizing basic mechanisms of actionof proposed neurotoxins. Two major interests of this project are: A) to define populations of individuals that may be at increased risk to neurological disease resulting from exposure to neurotoxins and B) to use naturally occurring variability in central nervous system function, anatomy and/or neurochemistry, to elucidate mechanisms of actions of neurotoxins. Several different projects have been investigated this year. (1) Interactions of the artificial food color, erythrosin B, with neuronal membranes and neurotransmission have been studied. Erythrosin B has been demonstrated, by several different criteria, to be a potent inhibitor of ATPase activity in brain and other tissues. Its inhibitory potency can be enhanced in vitro by exposing the tissue-erythrosin B complex to light. Studies are in progress to elucidate a possible "ligand-receptor" interaction between ATPases and erythrosin B. (2) Genetic and age variation in brain Na,K-ATPase are being investigated because they present a potential tool for elucidating the actions of erythrosin B on brain Na, K-ATPase. (3) Neuronal interactions between neuropeptides and dopamine D2 receptors in the basal ganglia are being studied to increase our understanding of the functional significance of dopamine defects in patients with Parkinson's disease and the therapies necessary for alleviation of their symptoms. (4) We are studying the effects of anticonvulsant drugs on adenosine A1 receptors to promote a better understnading of the actions of convulsant and anticonvulsant drugs. This new information should point out new directions for further biomedical research and lead to therapeutic improvements for these diseases.